Does Short‐Term Antiepileptic Drug Treatment in Children Result in Cognitive or Behavioral Changes?

Abstract

Summary:Purpose: To determine possible cognitive and behavioral effects of antiepileptic drug (AED) therapy by assessing children with newly diagnosed epilepsy before and after initiation of treatment. A comparison group of children with diabetes mellitus (DM) was included to control for the effects of practice, maturation, and chronic illness.Methods: Baseline neuropsychological assessments were completed for children with epilepsy (n = 37) and children with DM (n = 26) recruited through outpatient clinics at a regional children's hospital. Children were reevaluated 6 months from baseline testing. At follow-up, children with epilepsy had therapeutic AED levels and controlled seizures. Statistical analysis included a between-group repeated measures ANCOVA with pretest scores serving as the covariate.Results: Significant differences between groups were not found for any cognitive or behavioral factors, including attention (p < 0.24), immediate memory (p < 0.24), delayed memory (p < 0.10), complex motor speed (p < 0.19), or behavior problems (p < 0.89).Conclusions: Changes in performance on cognitive and behavioral measures were not different for children treated with AEDs and controls. Although adverse effects may be associated with prolonged treatment, results would not suggest adverse effects from AED monotherapy during the first 6 months of therapy. Key Words: Pediatrics-AnticonvuIsantsEpilepsy-Cognitive-Behavioral.Cognitive and behavioral effects of antiepileptic drugs (AEDs) remain a critical issue in the treatment of children with epilepsy. As acquisition of academic and social skills is rapid during childhood, adverse effects of AEDs may have a lasting impact on achievement and behavioral outcomes (1). In contrast to adults, children are less able to report effects of AEDs on their learning and behavior (2). Information is needed by parents, whose fears of negative side effects may reduce medical compliance, and by physicians, whose choice of a specific AED includes consideration of both medical efficacy and potential cognitive and behavioral side effects.Research concerning AED effects is marked by inconsistencies and contradictions. Phenobarbital has been the AED most frequently associated with cognitive and behavioral effects in children, including attentional difficulties, paradoxical hyperactivity, decreased short-term memory skills, and conduct disturbances (2-6). However, Mitchell et al. (7) reported minimal dose-related effects on attention, reaction time, and impulsivity at low

Neuropsychological status at seizure onset in children

“…In this study, neuropsychological assessment was not conducted as close to "onset" as it had been in other studies 9,10 ; however, age at onset in those studies was defined as a diagnosis of epilepsy following the second unprovoked seizure, so our studies might not be very different in this regard. Effect sizes were generally small, which suggests that the degree of neuropsychological impairment is subtle; however, these indices are attenuated to some degree by the restriction of range in cognitive dysfunction due to exclusion of children with early onset and IQ Ͻ70.…”

“…5 Supporting studies have been limited by small sample sizes (n ϭ 12-72 for most), [6][7][8][9][10][11][12][13] exclusion of seizure types/ etiologies, [6][7][8][9][10] long latencies between seizure onset and cognitive assessment, 7,8,12,14 using gross outcome measures 11,12,14 or testing limited functions, 6 no control group, 12,14 using retrospective report, 14 or ignoring prior unrecognized seizures, observed in one third of children. 15,16 Understanding risk factors for early neuropsychological deficiencies is critical for early intervention for common cognitive and academic comorbidities.…”

“…Estimated IQ spanned from borderline to superior; the mean and median IQs were typical of other studies. 9,10 Clinical characteristics and representativeness of the population. Most children had one seizure type; partial seizures were more frequent than generalized, characteristic of other studies, especially after age 5.…”

Practice parameter: Treatment of the child with a first unprovoked seizure

“…55 In one Class II study, 15 of 163 children assigned to AED withdrew because of intolerable side effects, 56 and in another, children taking PB did not show an expected increase in IQ on retest. 57 In three other studies, which included 48 children taking VPA, 1 taking PHT, and 51 taking CBZ, evidence was not seen of behavioral or cognitive impairment [58][59][60] (see table 5). A report from the American Academy of Pediatrics 44 regarding general recommendations for awareness of behavioral and cognitive effects of AED noted that high blood levels of some AED (PHT, PB, primidone) were significantly related to cognitive decline.…”

Academic performance in children with new-onset seizures and asthma: A prospective study

“…Although some early studies reported higher academic achievement for females than for males with epilepsy (16-18), others found no main effect for gender (7,19). In a recent study, Austin and colleagues (10) found males with high severity epilepsy to have the most risk for underachievement.…”